Lose 11% Body Fat in 8 Weeks W/Out Dieting Efforts!? The 'Egg-Approach' to Low CHO Dieting Quintuples Fat Loss

There are 1bn ways to prepare your eggs and the Internet is a rich source of recipes.

You will probably remember the SuppVersity news about the pro-anabolic effects of eggs - whole eggs - from the other day. Now, "gainz" are nice, but as a recent study from the University of Alabama at Birmingham indicates (Goss 2017), they are also a highly useful diet food.

In their recent experimental trial, Amy Miskimon Goss and colleagues investigated the effects of whole eggs, being consumed as part of a low carb diet on the diet-induced changes in body composition, body fat distribution and selected health parameters in aging men and women.

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For their randomized clinical trial, Goss et al. recruited 26 men and women aged between  60 and 75yrs. All subjects had a baseline BMI within the "obese" category (30–40kg/m²) and were randomly allocated to consume either ...

• an egg-based lower-CHO/high-fat diet (EBD) containing less than <25% of the energy from carbohydrates, more than 50% from fat and 25% of the energy from protein, or
• a standard CHO-based/low-fat diet (STD) with equal amounts of protein (25%), but 55% of the energy from carbohydrates and only 20% from fat

for 8 weeks. Interestingly enough, participants were not asked to restrict total energy intake. What they had to do, though was to eat the eggs or breakfast bars, the subjects in the EBD and STD group were provided with, respectively.

Figure 1: Overview of the macronutrient composition of the diets (Goss 2017).

The subject's body composition was measured by DXA, their resting energy expenditure (REE) by indirect calorimetry, and insulin, glucose, HOMA-IR and lipids by analyzing the blood of the subjects after an overnight fast, at baseline and after the 8-week intervention.

How did they lose weight if they didn't restrict their food intake? That all subjects lost significant amounts of body fat is a logical consequence of being provided with energy-sufficient meal plans thar reflect either a low-carb, high-fat or a high-carb, low-fat macro composition, when the baseline diet is an obesogenic Western Std. Diet with a high fat and high sugar content. In the absence of detailed food-logs to compare the pre-study intake with the food intake in the intervention study, we do yet have to base this assumption on previous evidence.

As you can see in Figure 1 (and probably already expected in view of the 'ad-libitum' approach), the subjects on the egg-based low carb diet lost more body fat (11.0% vs. 2.3% total fat | p<0.01 for the difference between diets).  Healthwise of even greater importance is that the EBD group also experienced ~3-fold greater loss in unhealthy visceral adipose tissue (aka 'organ fat') compared to the STD group (−23.3% vs −7.1%, p<0.01 for the difference between diets).

Figure 2: Relative changes in total and visceral body fat as measured by DXA scans performed before and after an 8-week high-fat, low-carb (blue) vs. low-fat, high-carb (orange) intervention W/ dietary restriction (Goss 2017).

Against that background, it's at best mildly surprising that the egg+low-carb diet also yielded significantly greater decrease in HOMA-IR (p<0.01); and that only the egg+low-carb group recorded significant decreases in triglycerides and increase in HDL. The changes in lean mass and the subjects' resting energy expenditure did not change.

And there's more new egg research... well, sort of "egg"

That adding eggs can do the most if you use them to replace refined starches and added sugar is also supported by another ahead-of-print paper. The 3-week cross-over (2-wk washout) study one comes from the Midwest Biomedical Research/Center for Metabolic and Cardiovascular Health Objective and evaluated the effects of a substituting refined starches and added sugars (16% of the total energy intake per day) with a combination of egg protein (Epro; 8% total energy intake) and unsaturated fatty acids (UFAs; 8% total energy intake) - which is basically a lower SFA version of eggs from free-ranging hens - on insulin sensitivity (primary outcome) and other cardiometabolic health markers in overweight or obese adults with elevated triglyceride (TG) concentrations.

Choline is also essential if you want l-carnitine to actually work | learn why

The choline advantage: One thing that clearly argues in favor of eggs, though, is that they are one of the best dietary sources of choline which is essential for your metabolic and cardiovascular health and a typical deficiency nutrient in "no egg"-diets (learn more). Furthermore, choline has been shown to promote fat loss when consumed in conjunction with caffeine and carnitine (see "Forgotten Dieting Aids") and stand-alone when it's taken during contest prep dieting (see "2g Choline Double Fat Loss").

As you can see in Figure 3, the twenty-five participants' [11 men, 14 women; mean ± SEM: age, 46.3 ± 2.4 y; body mass index (in kg/m²), 31.8 ± 1.0] Matsuda insulin sensitivity index (MISI) increased 18.1% ± 8.7% from baseline during the Epro and UFA condition and decreased 5.7% ± 6.2% from baseline during the carbohydrate condition (P < 0.001). Similarly, the disposition index (tests the function of the pancreas) increased 23.8% ± 20.8% during the Epro and UFA condition compared with a decrease of 16.3% ± 18.8% during carbohydrate (P = 0.042).

Figure 3: Changes in glucose metabolism and blood lipids (as marker of heart health) in recent crossover study of the effects of replacing refined carbohydrates (16% total energy) with egg-wite + PUFA (Maki 2017).

Of greater importance for heart vs. metabolic health was the incrase in LDL peak particle size of 0.12 nm with Epro and UFA that stood in contrast to a further worsening in form of a decrease of 0.15 nm with carbohydrates (P = 0.019). Similarly, TG and VLDL cholesterol concentrations were lowered by 18.5% (−35.7%, −6.9%) and 18.6% (−34.8%, −7.4%), respectively, after the Epro and UFA condition and by 2.5% (−13.4%, 17.0%) and 3.6% (−12.5%, 16.2%), respectively, after the carbohydrate diet condition (P < 0.002).

Three whole eggs also deliver the most effective "dose" of  egg yolk to improve your triglycerides ↓ and LDL ↓ but HDL ↑ | more

Bottom line: The study at hand stands in line with previous "egg studies" (read them), which highlight that eggs are a nutrient-dense, health-promoting superfood and not the bad "cholesterol bombs" as which they are still portrayed by both, the mainstream media, and "nutrition experts" who haven't upgraded their cookie-cutter approach to nutrition since the 1970s.

In spite of the previously mentioned evidence of the health benefits of eggs, I would like to remind you that other low-carb compatible high protein foods could have yielded similar effects.

It's also worth to note that, in line with previous studies, the effects of the egg diet cannot be ascribed to "any particular metabolic advantage [of low carb dieting] for body fat loss" (Hall 2017), but may be attributed to the ability of 'low carbing' to "decrease hunger, reduce appetite and promote satiety" (Hall 2017; Noakes 2017) - nevertheless, we cannot exclude that other foods with a similarly 50%/50% ratio of protein to fat and an "eggscellent" complete EAA profile could have worked just as well... at least until a follow-up study explicitly compares eggs to other low-carb foods show the opposite | Comment on Facebook!

References:

• Goss, Amy Miskimon, et al. "Effects of an Egg-based, Carbohydrate-restricted Diet on Body Composition, Fat Distribution, and Metabolic Health in Older Adults with Obesity: Preliminary results from a randomized controlled trial." The FASEB Journal 31.1 Supplement (2017): lb320-lb320.
• Hall, K. D. "A review of the carbohydrate–insulin model of obesity." European Journal of Clinical Nutrition (2017).
• Maki, Kevin C. et al. "Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or Obese Adults with Elevated Triglycerides." The Journal of Nutrition (2017) First published May 17, 2017, doi: 10.3945/ jn.117.248641
• Noakes, Timothy David, and Johann Windt. "Evidence that supports the prescription of low-carbohydrate high-fat diets: a narrative review." British Journal of Sports Medicine 51.2 (2017): 133-139.

Macros & Calories Don't Count? Better Food Choices Make Diet More Than 10x More Effective for PCOS Sufferers

Normal-weight women can have PCOS, too. Recently, Macruz et al. did DXA scans on young women with PCOS and a normal BMI and found increased truncal and leg fat compared to healthy controls in a similar age (12–39 years) and BMI range (at least 18.5 but below 25 | Macruz. 2017). More evidence that weight alone doesn't explain PCOS.

PCOS is by no means an issue only obese women suffer from. Yes, obesity is and will always be the #1 risk factor for developing the polycystic ovarian syndrome (PCOS = a condition in which a woman's levels of the sex hormones estrogen and progesterone are out of balance; this leads to the growth of ovarian cysts (benign masses on the ovaries); PCOS can cause problems with a women's menstrual cycle, fertility, cardiac function, and appearance), but eventually it seems as if both occurred in response to the same hitherto not fully elucidated triggers.

In that, it is unquestionable that a woman's diet plays a minor part in the development of PCOS. Accordingly, scientists all over the world are currently trying to determine the optimal diet for people like the 60 overweight or obese patients with PCOS who participated in a recent study from the Kashan University of Medical Science in Iran (Foroozanfard 2017).

Learn more about the (often ;-) small but significant difference at the SuppVersity

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The study was designed to evaluate the effects of the Dietary Approaches to Stop Hypertension (DASH diet) on weight loss, anti-Müllerian hormone (AMH) and metabolic profiles in women with polycystic ovary syndrome (PCOS). To this ends, the scientists conducted a randomized controlled clinical trial among 60 overweight or obese patients with PCOS. Patients were randomly assigned to receive either a low-calorie DASH (N=30) or control diet (N=30; designed to mirror the traditional Iranian diet) for 12 weeks. What is particularly interesting is that both diets had identical macronutrient compositions: 52-55% carbohydrates, 16-18% proteins, and 30% total fats.

Table 1: Constituents of the DASH and control diets in the study; data are presented for a calorie intake of 1800 kcal/day - (b) at least 3 servings of whole grains in the DASH diet; (c) low-fat (lower than 2%) in the DASH diet; (d) 4 servings of lean meat in the DASH diet and 2 servings in the control diet (Foroozanfard 2017).

However, the DASH diet was designed to be rich in fruits, vegetables, whole grains, low-fat dairy products, and low in saturated fat, cholesterol and refined grains (cf. Table 1). Both diets were equicaloric. Physical activity was monitored and identical in both groups. To further promote the comparability between the study arms, all subjects were...

The way we eat is not just obesogenic it is also acidogenic... or is the former just a consequence of the latter? Learn more!

[...] provided with 7-day menu cycles that were individually planned using a ‘calorie count’ system. To facilitate the compliance to the diets, participants were given and instructed an exchange list. 

[...] Compliance with the consumption of diets was controlled once a week through phone interviews. The compliance was also double-monitored by the use of 3- day dietary records completed throughout the study. 

[...] To control for dietary intakes of subjects throughout the study, the dietitian was calling the participants to resolve their probable problems" (Foroozanfard 2017).

The significant difference in the study outcomes you can see in Figure 1 are thus a function of the foods and not the macronutrient composition or the total energy intake of the women.

Figure 1: Anti-Müllerian hormone and metabolic profiles at baseline and after the 12-week intervention in women with polycystic ovary syndrome; p-values indicate stat. significance of the inter-group difference (Foroozanfard 2017).

More specifically, there was almost no change in glucose management in the control, but significant benefits in the DASH group; a further increase in the hallmark features of PCOS, i.e. anti-Müllerian hormone (AMH) and the free androgen index (FAI), but a significant decrease of these indices in the DASH group; and no change and a small improvement in heart-healthy NO and inflammation, respectively, in the control, but a huge increase in NO and decrease in inflammation (MDA) in the DASH diet group.

The detailed micronutrient breakdown shows that one of the reasons of the health benefits could be an increased intake of potassium, magnesium & co - eventually, that's yet not enough to explain the benefits of making better food choices - 'cause food ≠ macros.

Improving your health by eating healthy ≠ weight loss! Despite the impressive inter-group differences in all relevant health markers that were assessed in the study, the weight loss in both groups was identical, with the subjects' BMI dropping by -1.2±0.7 and -1.6±0.5 kg/m², respectively. That goes against the mantra that the best diet was always the one that produced the greatest weight-loss. Especially in people who are battling inflammation and insulin resistance, major health improvements can be achieved without concomitant weight loss... OK, usually you would expect anthropometric changes like a reduction in waist circumference as well as body and esp. visceral fat (Ehsani 2016; Orio 2016), but, unfortunately, these parameters were not assessed in the study at hand | Comment!

References:

• Ehsani, Behnaz, et al. "A visceral adiposity index-related dietary pattern and the cardiometabolic profiles in women with polycystic ovary syndrome." Clinical Nutrition 35.5 (2016): 1181-1187.
• Foroozanfard, Fatemeh, et al. "The effects of DASH diet on weight loss, anti‐Müllerian hormone and metabolic profiles in women with polycystic ovary syndrome: a randomized clinical trial." Clinical Endocrinology (2017).
• Macruz, Carolina F., et al. "Assessment of the body composition of patients with polycystic ovary syndrome using dual‐energy X‐ray absorptiometry." International Journal of Gynecology & Obstetrics (2017).
• Orio, Francesco, et al. "Obesity, type 2 diabetes mellitus and cardiovascular disease risk: an uptodate in the management of polycystic ovary syndrome." European Journal of Obstetrics & Gynecology and Reproductive Biology 207 (2016): 214-219.

Interaction of Fat Cell Size, Protein Intake & Co. W/ Fat Gain + Insulin Res. in Overfed Men + Women in Metabolic Ward

That's rather the low protein variety of overfeeding... but wait, was the high protein diet even "high" in protein? Well high enough to affect liver fat, for sure.

You will probably remember José Antonio's high protein overfeeding study series (learn more) from the articles here and on the SuppVersity Facebook page. The results were quite impressive, but the number of controlled covariates were small and the dietary control was limited to food logs.

In a more recent study, George A. Bray and colleagues from the Pennington Biomedical Research Center of the Louisiana State University System, the George Mason University, and the FL Hospital & Sanford-Burnham Prebys Discovery Research Institute (Bray. 2016) determined the effect of overfeeding diets with 5%, 15% or 25% energy from protein on glycemia + body fat distribution in healthy men and women with add. covariates and in a metabolic ward.

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In total, 15 men and 5 women were overfed by 40% (extra calories above maintenance) for 56 days with diets containing

• 5% (LP) of the total energy as protein, 
• 15% (NP) of the total energy as protein, or 
• 25% (HP) of the total energy as protein

Insulin sensitivity was measured using a two-step insulin clamp at baseline and at 8 weeks. Body composition and fat distribution were measured by DXA and multi-slice CT scan ... so far not so different, but the subjects were contained in a metabolic ward, cheating on the diet was thus as impossible, as taking supplements or working out like maniacs.

Figure 1: Diagram that illustrates the 8-weekstudy design; N = 10 male, 5 female subjects (Bray. 2016).

In conjunction with the scientists' analysis of the subjects abdominal subcutaneous fat cell size, which was determined on osmium fixed fat cells, these are two strengths of a study, of which it is yet quite obvious that it also had its disadvantages:

• 

  Review the effects of different macronutrients in overfeeding studies | more

  the protein content of the diet is simply hilarious - that's not just because eating 5% protein, only is nothing but idiotic, but also because 25% of protein is far away from what can be considered "high protein" these days;
• the lack of exercise limits the significance of the results - at least for the majority of SuppVersity readers overeating in phases in which you don't exercise is probably nothing they would even remotely consider.

The scientists observations that neither the subjects' insulin sensitivity and free fatty acids during low and high levels of insulin infusion did not differ after 8 weeks of overfeeding.

Figure 2: Effect of 8 weeks of overfeeding on abdominal fat distribution, ectopic lipid; rel. changes (Bray. 2016).

What did differ, however, were the changes in body fat distribution according to DXA and how the latter depended on the protein content on fat cell size before the overfeeding period. More specifically, ...

• the fat free mass (FFM) and intrahepatic lipid increased more on the high protein, whereas 
• % BF and fasting free fatty acids (FFA) increased more on the low protein diet, while

In addition, the scientists observed that a high initial fat cell size predicted increased visceral fat gains and the FFA suppression during the high-dose insulin clamp.

Figure 3: Relation of Baseline Fat Cell Size to Change in Visceral Adipose Tissue Mass with Eight Weeks of
Overfeeding in heathy volunteers (VAT 0.040 +/- 0.70(FCS); P < .0063 | Bray. 2016)

The subjects' insulin levels at baseline, on the other hand, predicted the increase in subcutaneous but not visceral fat accumulation (see Figure 3) - most intriguingly with low fasting insulin
at baseline correlated predicting higher changes in % fat (for insulin the scientists observed a correlation with r = –0.43; P < .034), but not with other variables. It is thus not surprising that the most insulin sensitive subjects also gained the most subcutaneous fat... or, as the scientists put it: "HOMA IR predicted the increase in DSAT (r = 0.50; P <.016), but not other variables" (Bray. 2016).

Those are important insights of which the authors rightly point out that they clearly indicate that "an induction of insulin resistance with overfeeding is related to fat cell size and requires more than an expansion of adipose tissue stores" (Bray. 2016).

A surprising, but not debatable result of the study at hand is that the high protein diet increased liver fat (HUs;  measured with DXA, too).  The low protein diet, on the other hand, helped to decrease the subjects' liver fat significantly - remember: we are talking about a diet with 40% extra energy on top of the regular diet (Bray. 2016).

Bottom line: Yes, you've read all that in individual articles (albeit often about rodent studies) on SuppVersity before: (1) the more protein, the greater the lean mass gains; (2) the less protein, the greater the ratio of fat to lean mass gains; (3) the fuller your fat cells, the more likely you will gain metabolically unhealthy visceral fat; and (4) the more insulin sensitive you still are, the more metabolically healthier subcutaneous fat you will gain.

What is news, or at least has not been observed in Antonio's study in active individuals (also because they didn't look) is the surprisingly ill effect of high amounts of protein on liver fat (see Figure, right): while the low protein diet reduced the subjects' liver fat sign, the high protein diet triggered a small, but undesirable accumulation of liver fat during overfeeding in normal-weight subjects - not good, but not yet critical and hopefully something you'd not see w/ concomitant exercise or smaller calorie excess | Comment!

References:

• Bray, George A., et al. "Effect of three levels of dietary protein on metabolic phenotype of healthy individuals with 8 weeks of overfeeding." The Journal of Clinical Endocrinology & Metabolism (2016): jc-2016.

Is Lard More Fattening Than Hydrogenated Vegetable Oil!? 17% Extra Weight, 32% Extra Fat Gain + Increased Appetite

Not all fats are created equal and lard and hydrogenated vegetable oils are not on the top-list of "healthy fat choices".

Our perspective on fat has changed significantly over the last decade. While some people still propagate that "fat is bad" and "should be generally avoided", most experts have stopped bashing fat in general and are now focusing on saturated fats. Saturated fats as they occur in lard,.. but wait! If you take a closer look at the fatty acid composition of lard, it turns out that it contains "only" 39.2% saturated, but 45.1% mono- and 11.2% polyunsaturated fats. That's actually not too far off of the average vegetable shortening with a saturated to monounsaturated to polyunsaturated fat ratio of 25.0 / 41.2 / 28.1% (nutritiondata.com)

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In contrast to said even more dreaded partially hydrogenized vegetable fats, which contains a whopping 13.2g of transfats per 100g, lard is yet mostly trans-fat free. That's a good thing, right? After all, high trans-fat intakes have been associated with increased inflammation and cardiovascular disease  (Hu. 1997; Lopez-Garcia. 2005. Now, while experimental evidence confirming negative effects in humans is non-existent, negative effects have also been observed in controlled animal experiments. It is thus more than reasonable to assume that of two of the most commonly used fat sources for cooking, i.e. lard and hydrogenated vegetable-shortenings, the former, the trans-fat free 100% "natural" fat source should be the healthier one.

Figure 1: Fatty acid content (g) of the three test diets (Kubant. 2015)

To check the validity of this hypothesis, scientists from the University of Toronto fed male Wistar rats for 14 weeks diets which contained either (1) high vegetable fat (HVF, 60 kcal% from vegetable shortening) or (2) high lard fat (HLF, 60 kcal% from lard). A group of rats that received the normal-fat chow (NF, 16 kcal% from vegetable shortening) served as control (see Figure 1). Body weight, food intake, adipose tissue mass, serum 25[OH]D3, glucose, insulin and fatty acid composition of diets were the scientists' main outcome data - data that confirm that not everything we take for granted will actually stand the test of science.

Figure 2: Body weight and fat gain over 12 weeks on control (low fat) or high fat diets w/ lard (HLF) or hydrogenated vegetable oils (HVF) as main fat sources (Kubant. 2015).

In contrast to what common sense would dictate, the rodents in the lard group were not leaner and healthier. In fact, the data in Figure 2 tells you that the exact opposite was the case: The rodents on the high lard diet gained significantly more body weight and - more importantly - body fat and did not, as some may now speculate, simply store the extra energy away instead of having it float around in the blood and ruin their insulin sensitivity (see Figure 3).

Figure 3: Markers of glucose metabolism at the end of the study (data expressed relative to control | Kubant. 2015)

So, basically, the scientists, who had even speculated that lard, due to its naturally high vitamin D content "may act to reduce the metabolic consequences associated with obesity, as suggested by other investigators" (Kubant. 2015), had to realize that their prediction was wrong. Whether lard is simply unhealthier or whether the effect was a results of the comparably lower food intake of the vegetable shortening group is difficult to say. What we do know, however, is that the animals who were on the lard diet consumed more calories than the HVF group. That 1g/day of extra food, however, was enough to have the scientists conclude that the rats have a strong preference for the taste of fat sources containing long-chain fatty acids (that is, oleic and linoleic), but by no means enough, to fully explain the significant difference in weight and body fat gain.

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So lard is much worse than transfats? I wouldn't dare making a general statement about lard vs. vegetable shortenings based on this study. One thing I would like to remind every saturated animal fat worshipper of, however, is that his beloved "saturated fat sources" like lard are in fact hardly saturated at all. The common lard, the scientists used in the study at hand, for example, has higher amounts of polyunsaturated fatty acids in it than the average vegetable shortening. Its (by the saturated fat lovers dreaded) content of omega-6 fatty acids in the form of linoleic acid, which is currently everybody's favorite scapegoat for being obese, diabetic or whatnot, is even three times higher!

What we must not forget, either, are the divergent results about the fattening effects of transfats from monkey and rodent studies. While the one existing monkey study showed higher levels of intra-abdominal adiposity and insulin resistance in monkeys fed trans fatty acids (TFAs) for 6 years under a controlled feeding regimen (Kavanagh. 2007), a more recent study in rats found that dietary TFAs fed ad libitum (as much as the rodents wanted) did not influence food intake or body fat accumulation (Ochiai. 2013). Now, monkeys are more reliable than rats, right? Well, yes, but if the monkeys are on an energy restricted and the control diet was no lard diet, but rather the "perfect monkey diet", the rodent study with its realistic ad-libitum access to food and a diet composition that was more akin to what people eat these days becomes increasingly attractive. Overall, however, it doesn't really make sense to use any of these studies to speculate about the practical significance Kubant's rodent study has for men. If you asked me, it is not even relevant, anyways, because neither lard nor hydrogenated vegetable oils should be a regular part of your diet | Learn why in a previous SuppVersity Article or tell me what you think on Facebook!

References:

• Hu, Frank B., et al. "Dietary fat intake and the risk of coronary heart disease in women." New England Journal of Medicine 337.21 (1997): 1491-1499.
• Kavanagh, Kylie, et al. "Trans fat diet induces abdominal obesity and changes in insulin sensitivity in monkeys." Obesity 15.7 (2007): 1675-1684.
• Kubant, R., et al. "A comparison of effects of lard and hydrogenated vegetable shortening on the development of high-fat diet-induced obesity in rats." Nutrition & Diabetes 5.12 (2015): e188.
• Lopez-Garcia, Esther, et al. "Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction." The Journal of nutrition 135.3 (2005): 562-566.
• Ochiai, Masaru, et al. "Effects of dietary trans fatty acids on fat accumulation and metabolic rate in rat." Journal of oleo science 62.2 (2013): 57-64.

Niacin (B3) & Glucose Management | Part V of the "There is More To Glucose Control Than Carbohydrates"-Series. Plus: Can You Use Niacin to Ramp Up Fat Burning During Fasts?

Some scientists speculate that the niacin could be the root cause of the diabesity epidemic. Others believe it's the solution.

After last the installments on vitamin D and calcium, I decided that it would be about time to talk about a nutrient with (purported) negative effects on blood glucose management. After some serious head-scratching I chose niacin aka nicotinic acid and it's innocent brother niacinamide for today's fifth installment of the  my choice "There is More To Glucose Control Than Carbohydrates"-Series.

Even if you haven't been following the SuppVersity articles over the last years, you will probably be aware of some of the health effects high and low vitamin B3... ha? Right! Niacin is the only vitamin with proven HDL boosting effects (van der Hoorn. 2008).

You can learn more about this topic at the SuppVersity

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Flush & No-Flush Niacin & Diabesity

There is more to come!

The patented slow-release version "Niaspan" is often administered in conjunction with statins to patients with hypercholesteremia - quite successfully, actually... well, at least if you discard the debilitating effects both statins and slow release niacin can have on your musculature - as a series of case-reports from the Mayo Graduate School in Rochester and the Cardiovascular Institute in New York shows, even when niacin is administered without additional lipid-lowering drugs (Litin. 1989; Gharavi. 1994 | please keep in mind that all patients in these studies were well beyond 60 and high blood lipids were not their only health problems)... but I am losing sight of our actual topic.

It's not all about blood lipid management 

While the (albeit low) risk of niacin-induced myopathies have gained only minimal attention among the research community, early reports of niacin induced insulin resistance and an significant increases in fasting blood sugar in diabetes patients on Niaspan therapy (Garg. 1990), on the other hand, have lead to a marginalization of niacin as a standalone treatment of which more recent studies would suggest that they are more or less unwarranted (Grundy. 2002).

In a 16-week, double-blind, placebo-controlled trial with 148 patients who were randomized to placebo (n = 49) or 1000 (n = 45) or 1500 mg/d (n = 52) of extended release niacin (47% of the patients were on statins at the same time), Grundy et al. found that the "rates of adverse event rates other than flushing were similar for the niacin and placebo groups" and conclude that, even in type II diabetics, "[l]ow doses of ER niacin (1000 or 1500 mg/d) are a treatment option for dyslipidemia." (Grundy. 2002)

Niacin & glucose metabolism beyond metabolic syndrome

In view of the fact that I hope that only a small minority of you will (still) belong to the group of patients doctors ans scientists usually lump together as patients suffering from "metabolic syndrome", I would suggest we steer away from the niacin for cholesterol management issue and assume a more glucose-specific perspective to decide, whether or not niacin and/or niconamide supplements or fortified foods could compromise your glucose sensitivity.

To this ends, it may make sense to take a close look at the mechanism that's responsible for the previously described increase in blood glucose in type II diabetics and the significant reductions in of the glucose infusion rate Kelly et al. measured in a study with healthy 7 healthy volunteers who had been consuming 500 mg daily nicotinic acid (=regular niacin) for 7 days then 1 g daily for a further 7 days in euglycemic clamp scenario (Kelly. 2002).

What's the mechanism?

It is generally accepted that the negative effects of niacin are mediated by its interaction with the GPR109A receptor. What scientists still argue about is, whether the effects of the ingestion of high amounts of niacin (not niacinamide, by the way!) are of direct or indirect nature. 

Now, contrary to common believe, science is actually a very simple business. In physics, specifically, history has told us that it's usually the simpler of two competing hypothesis that's the right one. Against that background it's not unlikely that the negative effects of niacin aka nicotinic acid (pyridine-3-carboxylic acid, cf. Guyton. 2007) are nothing but the mechanistic profound changes in the amount and handling of blood lipids.

Figure 1: Illustration of the niacin induced changes in FFA (initial drop and rebound after 2h); levels were measured in healthy normolipidemic volunteers after the ingestion of 2g of regular niacin (Wang. 2000)

For you as a diligent reader of the SuppVersity it should not be too difficult to see that it's the FFA / TG pin-pong that's brought up by niacin's ability to suppress the release of free fatty acids via its interaction with the GPR109A receptor which is at the heart of the acute impairments in glucose uptake (Offermanns. 2006 | recent studies have shown that this effect is accompanied by a stimulation of adiponectin production, an adipokine with beneficial effects on glucose metabolism; cf. Plaisance. 2009).

Figure 2: Consider the growth hormone release in response to the administration of niacin and the drop of free fatty acids an "added bonus" - not a growth bonus, but certainly one that will increase the liberation of bound and oxidation of free fatty acids (data based on Quabbe. 1983).

Can you (ab-)use niacin during (intermittent) fasts? Actually, I have been thinking about ways to (ab-)use the rebound effect that occurs with large (>1,000mg of niacin - in people at risk of developing type II diabetes, even niacinamide; cf. Greenbaum. 1996) for quite some time now. Someone who is "intermittent fasting", for example, should be able to ingest a large amount of niacin before a low(-ish) fat, high carb meal (e.g. after a workout) should actually benefit from the low free fatty acid & triglyceride levels in the blood (Usman. 2012) and the corresponding increase in insulin sensitivity / glucose uptake (Boden. 1997) and give a damn about the free fatty acid rebound that occurs a couple of hours later (Kamanna. 2008). In healthy individuals, the sudden appearance of large amounts of free fatty acids in the blood stream would even ramp up fatty oxidation and thus increase the energy availability during the fast - wouldn't be too bad, don't you thinks so?

Blood lipids up, glucose tolerance down! It's as easy as that and in the end a result of the way our bodies react to the overabundance of a certain type of energy source by prioritizing its usage of that of another one; and during the free fatty acid rebound that occurs ~2-3h after the ingestion of nicotinic acid the overabundant energy source if fat.

As the words "temporary" and "adaptation" in the previous sentence already suggest, this does not necessarily have to be a bad thing. I mean, as long as you don't stuff yourself with carbs during this 3h+ "fat flood" (the actual length depends on the dosage and will vary from person to person), your fasting blood glucose levels will remain stable.

Figure 3: Correlation between diabetes & obesity prevalence (left) and per capita niacin intake (mg/day) and obesity prevalence in US adults (right) from 1920 to 2000 (Zhou. 2010)

Against that background it is in my humble opinion unwarranted to speculate about a causal nature of the the correlation between the increased diabetes and obesity ratesm on the one hand, and the average per capita niacin intake of the average American you can see in Figure 3 - and that in spite of rodent studies by the same researchers which suggest that "long-term high nicotinamide intake (e.g. induced by niacin fortification) may be a risk factor for methylation- and insulin resistance-related metabolic abnormalities" (Li. 2013).

In view of the fact that grains (flour and cereals) are the most widely used vehicles for niacin-fortification, it should be obvious that the over-consumption of over-processed, but fortified junk foods, and not the relatively small amounts of extra niacin in this "foods" are much more likely to explain the increased prevalence of obesity in US adults and children, Zhou et al. and Li et al.seek to explain by a "chronic niacin overload" in their 2010 papers in BMC Public Health (Zhou. 2010) and the World Journal of Gastroenerology (Li. 2010).

On the other hand...

Moreover, we are, as usual, dealing with conflicting evidence, some of you may actually remember from the SuppVersity Facebook News (like www.suppversity.com/facebook and make sure you always stay ahead of the game | read the corresponding news item on niacin). In a rodent model of obesity and type II diabetes, a group of scientists from South Korea observed small, albeit significant increases in glucose tolerance in response to the administration of both high dose niacin (NA) and niacinamide (with niacinamide > niacin; Yang. 2014).

Figure 4: Changes in blood glucose, insulin, HOMA-IR and triglyceride levels in response to 10/100mg of niacin (NA) or niacinamide (NAM) in a rodent model of obesity and type II diabetes (Yang. 2014)

And while both nicotinic acid (niacin) and niacinamide led to improvements in insulin sensitivity (= reduced HOMA-IR), the latter lead to significant increases in triglycerides which stand in contrast to the triglyceride lowering effects of nicotinic acid.

In addition to that, there is evidence that niacin and nicotinamide decreases high glucose-dependent oxidative stress (Ye. 2011; Torres-Ramírez. 2013). What we don't have though, is reliable evidence from controlled human studies to support this Janus-faced nature of "niacin" and the purported benefits of high dose niacinamide supplementation:

• Reduced incidence of type I diabetes: Although this would appear to be rather an auto-immune issue, the net consequences of the results of a population‑based diabetes prevention trial that was conducted on school children aged 5‑7.9 years are obviously of utmost importance for glucose control (Elliott. 1996). The kids who received sustained‑release
  niacinamide 1.2 grams/m² (body surface area) per day for an average of 7.1 years had a
  lower incidence of T1DM versus controls.
• Niacinamide may also have protective benefits in T2DM. A single blind study of 18 diabetic patients found that niacinamide improves C‑peptide release leading to a metabolic control similar to patients treated with insulin (Pozzilli. 1996).
  
  The patients had been assigned for 6‑month to either: (1) insulin plus nicotinamide (500 mg three tablets/day); (2) insulin plus placebo (3 tablets/day) and (3) current sulphonylureas plus nicotinamide (500 mg three tablets/day). Compared to the placebo group, C‑peptide release increased in both the insulin/niacinamide and sulphonylureas/niacinamide groups, while HbA1C, fasting and mean daily blood glucose levels improved in the three groups to the same extent.

Eventually, I would thus be hesitant to recommend using amounts of 1,500mg of niacinamide or niacin / nicotinic acid (the terms are used inter-changeably) per day as a strategy to prevent the development of type II diabetes. If you stay active and stay away from the niacin-fortified junk Zhou and Li failed to recognize as the common denominator of the increases in niacin intake, obesity and diabetes, you don't need it anyway.

Figure 5: The increases in HOMA-IR Westphal et al. observed in response to the administration of 1g/1.5g of niacin in patients with high LDL and low HDL levels look more severe than they actually are - in fact, they did not even achieve statistical significance. In contrast to the beneficial effects on adiponectin and HDL (Westphal. 2006)

Bottom line: Our regular niacin intake, as well as the comparatively low amounts of niacin and niacinamide in multi-vitamins and other useless supplements are not going to push you over the diabetic edge. As far as high dose supplements are concerned, we will probably have to distinguish between extended release (ET) preparations, which would be used for lipid management and immediate release forms of niacin and nicotinamide.

The extended release (ET) preparations appear to be useful as lipid lowering drugs. Their effects on blood glucose management are yet either neutral or negative (). High amounts of the "regular", flush-niacin, will produce a free fatty acid rebound and transient impairments in insulin sensitivity, of which I would like to see if you they cannot be used to your advantage (see infobox "Can you (ab-)use niacin during fasts?". Unlike ET and "flush" niacin, nicotinamide does not interact with the GPR109A receptor (Soga. 2003; Tunaru. 2003; Wise. 2003) and will thus neither produce free fatty acid rebounds nor will it raise your HDL, adiponectin and leptin levels (Westphal. 2006 & 2007; see Figure 5). In other words, it's benign, but useless - this is at least what we have to assume until there is convincing evidence from human studies outside of type-I-diabetes scenarios as they were described by Elliott (1996) or Pozzilli (1995).

References:

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