|Some scientists speculate that the niacin could be the root cause of the diabesity epidemic. Others believe it's the solution.|
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).
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)|
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)|
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)|
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.
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- Tunaru, Sorin, et al. "PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect." Nature medicine 9.3 (2003): 352-355.
- Usman, M. Haris U., et al. "Extended-release Niacin Acutely Suppresses Postprandial Triglyceridemia." The American journal of medicine 125.10 (2012): 1026-1035.
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- Yang, Soo Jin, et al. "Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes." The Journal of nutritional biochemistry 25.1 (2014): 66-72.
- Ye, X., et al. "Niaspan reduces high-mobility group box 1/receptor for advanced glycation endproducts after stroke in type-1 diabetic rats." Neuroscience 190 (2011): 339-345.
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