Along with lifting your heart …
The spectrum of benefits for
vitamin B3 has widened
The vitamin-deficiency disease pellagra was first identified in 1735 by Spanish physician Gaspar Casal. Considered to be Spain’s first epidemiologist, Casal is famous for his clarity and independence of thought, along with his conceptual change in the approach to medicine. Instead of mere observation and reporting, Casal moved to a fact-based induction methodology, presaging the work of John Stuart Mill, the political philosopher, economist, and logician, one hundred years earlier.
In the 18th century, Spain embraced the Age of Enlightenment, directing the beacons of thought to all endeavors. But while Spain was not as advanced as France, Britain, Germany, or America, its new political thinking led to the revocation of most of the historical rights and privileges of the sub-kingdoms that comprised the Spanish Crown. Those changes, in turn, allowed for the freedom of inquiry that was so needed for medical discovery, among others.
The Progression of Niacin Discoveries
Returning to pellagra, Dr. Casal was the first to offer a clinical description of the disease. He called it mal de la rose due to the red rash seen on the hands and feet of sufferers. In fact, his account is now recognized as the first modern pathological description of a syndrome. This was the beginning of a progression of discoveries that led to the isolation of niacin in 1911, and its direct implication as the dietary deficiency factor in pellagra in 1937.
Casal is famous for his clarity and
independence of thought. In fact, his
account of pellagra is now recognized
as the first modern pathological
description of a syndrome.
In the 1700s, pellagra was an endemic disease in northern Italy—which had not been known until maize (corn) was introduced from America. Italy gave the disease the name, “pelle agra” (pelle means skin; agra means rough). Casal had observed that patients with pellagra were all poor, subsisted mainly on maize, and rarely ate fresh meat. Because pellagra outbreaks occurred in regions of Europe where maize was a dominant food crop, the belief was that maize either carried a toxic substance or was a carrier of disease. When it was later noted that there were few pellagra outbreaks in Mesoamerica, where maize is a major food crop (and is processed), it was considered that the causes of pellagra may be due to factors other than toxins.
Making Niacin Nutritionally Available
In the New World, maize was traditionally treated with lime, an alkali now shown to make niacin nutritionally available and thereby reducing the chance of developing pellagra.1 However, when in the 18th century corn cultivation was adopted worldwide, treatment with lime was not accepted because the benefit was not understood. Thus in the New World, often heavily dependent on corn, cultivators rarely suffered from pellagra, which became common only when corn became a staple that was eaten without the traditional treatment. Of interest, if maize is not so processed, it is a poor source of tryptophan as well as niacin.
Before Statins, There was Niacin
Hypercholesterolemia (high cholesterol) is one of the main risk factors in the development of atherosclerosis, a condition that with the development of statins over the last 20 years has become more treatable, but not without consequences. Statins have been shown to reduce the incidence of cardiovascular events by 25–40%, yet this reduction is no big deal, especially considering that many patients need additional therapy to reach more optimal lipid levels and prevent cardiovascular events.
Besides that, dyslipidemia (and hypercholesterolemia in particular), remain undertreated in many patients diagnosed with coronary artery disease. High triglycerides, a contributor to cardiovascular dysfunction by many but not all studies, are somewhat treatable with fibrates, yet there are significant limitations for their use. Elevated fasting triglyceride levels have been shown to be a strong risk factor for ischemic heart disease, independent of other known risk factors for atherosclerosis.
In addition to lowering low-density and total cholesterol along with triglycerides, increasing high-density lipoprotein cholesterol (HDL-C) has become one of the principal objectives for treating hyperlipidemia. Considerable evidence has shown that even a minor improvement in HDL-C levels may significantly reduce cardiovascular risk. For example, it has been found that an increase of 1 mg/dl in HDL-C levels results in a parallel reduction in coronary artery disease risk by 2% in men and 3% in women. Moreover, HDL-C helps to transport oxidized cholesterol from peripheral tissues where it instigates atherosclerosis to the liver for excretion. Furthermore, HDL-C has potential anti-inflammatory, anti-thrombotic and anti-oxidant effects.
Niacin is another class of lipid-lowering agents, about which research dates back at least 55 years.2 Not only does niacin lower low-density lipoprotein (LDL-C, the “bad” cholesterol), total cholesterol, and triglycerides, it increases HDL-cholesterol (HDL-C, the “good” cholesterol) by inhibition of lipolysis in adipose tissue, which eventually leads to improvement in all lipid parameters. Furthermore, there are studies suggesting that niacin can improve the clinical outcome in cardiovascular disease, and that it may lead to the regression of atherosclerotic plaque. Dyslipidemia is closely related to erectile dysfunction (ED) and evidence has shown that statins can improve erectile function. However, the potential role of that other lipid-lowering agent, niacin, hasn’t been known until now.
Niacin for Erectile Dysfunction
In a new study, researchers set out to assess the effect of niacin alone on erectile function in patients suffering from both ED and dyslipidemia.3
Using the protocol of a clinical randomized placebo-controlled parallel-group trial, the study also took place at the University of Hong Kong. One hundred sixty male patients with ED and dyslipidemia were randomized into two groups receiving either up to 1,500 mg of oral niacin daily or placebo for 12 weeks. Using questions from the International Index of Erectile Function (IIEF, particularly questions Q3 and Q4), the primary outcome was improvement in erectile function. Q3 ranked “frequency of penetration,” while Q4 ranked “frequency of maintained erections after penetration.” Other outcome measurements included the total IIEF score, IIEF-erectile function domain, and Sexual Health Inventory for Men (SHIM) score.
In the New World,
maize was traditionally treated
with lime, an alkali, now shown to
make niacin nutritionally available
and thereby reducing the
chance of developing pellagra.
In the analysis of the study, the niacin group showed a significant increase in both IIEF-Q3 scores and IIEF-Q4 scores compared to the initial baseline values. While the placebo group also showed a significant increase in IIEF-Q3 scores (high hopes, no doubt), it did not for IIEF-Q4 scores. In other words, the “placebo effect” did not extend to maintaining erections. Also, when patients were stratified according to the baseline severity of ED, the patients with moderate and severe ED who received niacin showed a significant improvement in IIEF-Q3 scores (0.56 and 1.03, respectively) and IIEF-Q4 scores (0.56 and 0.84, respectively) compared with baseline values. These results were not significantly increased for the placebo group.
Best Results: Severe and Moderate ED
The improvements in IIEF-erectile function domain (IIEF-EF) score for moderate and severe ED patients in the niacin group were 3.31 and 5.28 and in the placebo group were 2.74 and 2.65, respectively. In the lower range of mild and mild-to-moderate ED, there was no significant improvement in erectile function. Of the 160 patients in the study, 32 were using statins; 18 in the niacin group and 14 in the placebo group. For patients not receiving statin treatment, there was a significant improvement in IIEF-Q3 scores (0.47) for the niacin group, but not for the placebo group. To summarize, niacin alone can improve the erectile function in patients suffering from moderate to severe ED and dyslipidemia.
Intelligence Lifted and Enlightened
Nothing like the Spanish Enlightenment had occurred since the Spanish Renaissance (starting around 1492, the year that Columbus set sail for the New World), which like the Italian Renaissance was inspired by Classical antiquity and especially the Greco-Roman tradition in the arts, literature, and science.
Unfortunately, many of the same factors that brought the Italian Renaissance to an end—among them corruption, wars, and a widespread backlash over secularism and indulgence (leading to the “Bonfire of the Vanities”)—also terminated the “rebirth” in Spain. Chasing heresies became a sport that led to the resurrection of the Inquisition, which unlike its prior appearances operated completely under royal authority, rather than the aegis of the church.
The Enlightenment proved itself to be an intellectual movement in 18th Century Europe that mobilized the power of reason to advance knowledge and reform society. It promoted intellectual transaction and opposed intolerance and abuses by both Church and State. This constituted a challenge to and disparagement of the heavy-handedness of the State. Thus, society was lifted and enlightened.
Motivated by philosophers that included John Locke (the most influential of Enlightenment thinkers), Voltaire, Newton, and Leibniz, ruling princes throughout Europe endorsed and fostered the intelligentsia of the Enlightenment. Some of these rulers even attempted to apply the ideas of the enlightenment to government. When grasped by “natural aristocrats,” the Enlightenment was particularly successful in America where it influenced Benjamin Franklin and Thomas Jefferson, among many others, and fueled the fires that led to the American Revolution, the Declaration of Independence, and the creation of the United States.
Toleration Despite Adversity
There was a higher incidence of adverse events in those taking niacin. However, most patients could tolerate it at the maximum dosage (1,500 mg/day). With this in mind, niacin could be an alternative choice of treatment for patients with ED. Despite the success of phosphodiesterase type 5 inhibitors (PDE5 inhibitors), such as sildenafil, only around 60–70% of patients have a satisfactory response to this class of drugs. And there are adverse effects such as headache, flushing, dyspepsia, nasal congestion, and impaired vision, including photophobia and blurred vision. Hence, there is a need to develop other therapeutic agents for those patients who do not respond satisfactorily to PDE5 inhibitors or are contraindicated for those such as sildenafil.
Erectile Function Related to Metabolic Syndrome
It is now thought that ED is part of the cardiovascular disease complex related to metabolic syndrome (MS). Although endothelial dysfunction and atherosclerosis are believed to be part of the main mechanisms for ED in patients with MS, other mechanisms account for ED in MS include androgen deficiency, drugs, the veno-occlusive mechanism, etc. Because dyslipidemia is one of the key risk factors for the development of endothelial dysfunction and atherosclerosis in MS patients, there is a close relationship between ED and dyslipidemia.
In fact, dyslipidemia is commonly found in ED patients, and studies show that statins can help to improve the response of PDE5 inhibitors in those suffering from ED precisely because they improve atherosclerosis. Consequently, statins can be used as a treatment in patients with an unsatisfactory response to PDE5 inhibitors, yet there are problems with statins too, among them raised liver enzymes and muscle problems, some of which can be quite serious and even deadly (rhabdomylosis).
Niacin May Directly Affect the Principal Erectile Mechanism
In the Hong Kong study, the researchers postulated that niacin might be as beneficial as statins on erectile function, and have other related benefits too. Niacin is known to produce a flushing effect (see “Toleration Despite Adversity,” above), which is related to prostaglandin D2 (PGD2) release in the skin. This can lead to vasodilation and concomitant flushing. The production of PGD2 can also occur in macrophages, a type of protective white blood cell. Consequently, when PGD2 production is induced by niacin, it may affect all body tissue, including the cavernosal tissue in the penis. Indeed, PGD2 is one of the potential agents causing the vasodilation and engorgement of cavernosal tissue, thereby leading to erection. Thus, niacin improves erectile function by stimulating the production of PGD2.
Because dyslipidemia is one of
the key risk factors for the
development of endothelial dysfunction
and atherosclerosis in MS patients,
there is a close relationship between
erectile dysfunction and dyslipidemia.
The principal difference between the Hong Kong study. and others that proceeded it, is that the researchers used niacin alone, rather than in combination with PDE5 inhibitors. The results indicate that niacin can improve erectile function in those with moderate to severe ED but not in those with mild and mild-to-moderate ED. Statins also appear to be effective for improving erectile function in those with more severe ED.
Niacin Instead of Statins
The researchers reasoned from other studies that when the degree of endothelial dysfunction and atherosclerosis are more severe, the effects of niacin and statins as lipid-lowering agents are also more apparent. Their current study seemed to bear this out. Also, in another study assessing the effect of a PDE5 inhibitor in patients using a statin, patients with higher baseline serum LDL-C had better improvement in erectile function after the use of a PDE5 inhibitor. This supports the researchers’ hypothesis that patients with potentially more serious endothelial dysfunction, such as those with higher LDL-C levels, may have better response to the combination usage of a PDE5 inhibitor and niacin.
The Hong Kong study is the first to
examine the effects of niacin alone,
without the concomitant use of a
PDE5 inhibitor, such as sildenafil.
Besides, niacin’s beneficial effects became more evident when the Hong Kong study researchers excluded those already using statin therapy. If there is an overlapping effect of these two groups of lipid-lowering agents on endothelial function, this would make sense. Also, chronic statin use could lessen the effect of niacin on endothelial function and hence affect improvement in erectile function.
Can Niacin Help with ED if Lipids are Normal?
Because the study included only subjects with dyslipidemia, the results may not be applicable to those with ED who have a normal serum lipid profile. Furthermore, patients using aspirin or NSAIDs were excluded to avoid the effect of these drugs in inhibiting prostaglandin D production, which may be one of the potential mechanisms for the effects of niacin on ED. It should be noted that it is quite common for ED patients to have coexisting cardiovascular disease that requires the use of aspirin. Therefore, further study on the interaction of aspirin and niacin in ED patients may be needed to establish the role of niacin in clinical usage.
Also to be considered, patients were not using PDE5 inhibitors during the study period. Therefore it wasn’t determined whether the combined use with niacin can enhance the response of PDE5 inhibitors. Another limitation on the study results was the exclusion of the partner’s assessments. This would help to provide a more comprehensive assessment of the efficacy of niacin.
Finally, while a 12-week regime of niacin treatment found beneficial effects in ED patients, the potential benefit of long-term use of niacin for ED is not known. Further studies would help to determine the optimal treatment period for niacin usage in ED patients.
For the First Time
In the end, the data from the Hong Kong study suggest that niacin alone can improve the erectile function of subjects with dyslipidemia suffering from ED. This is the first time this conclusion has appeared in the literature. Once again, the effect of niacin is clinically significant in those with moderate to severe ED. Further, because of the close relationship between ED and dyslipidemia, niacin could prove to be an important therapy for managing both conditions. Who knows? There may even be other benefits. Future studies will further refine the indications and benefits of niacin in patients with ED.
Niacin alone can improve the
erectile function of subjects with
dyslipidemia suffering from
Lastly, it should be remembered that many individuals without dyslipidemia take niacin as a preventative measure. If you plan to take more than about 800 mg of niacin a day, it is a good idea to have your liver tested periodically just to make sure that your liver has no problem with high-dose niacin. These liver tests are the same used to check for liver toxicity in people taking statins, from which there is a higher likelihood of liver toxicity compared to taking niacin. The principal problem from taking statins is muscle damage which is serious enough to be life-threatening. This problem does not occur with those who take niacin. Not to be forgotten, niacin has been found to prolong orgasm.
- Rajakumar K. Pellagra in the United States: a historical perspective. South Med J 2000 Mar;93(3):272-7.
- Parsons WB Jr, Achor RW, Berge KG, Mckenzie BF, Barker NW. Changes in concentration of blood lipids following prolonged administration of large doses of nicotinic acid to persons with hypercholesterolemia: preliminary observations. Proc Staff Meet Mayo Clin 1956 Jun 27;31(13):377-90.
- Ng CF, Lee CP, Ho AL, Lee VW. Effect of niacin on erectile function in men suffering erectile dysfunction and dyslipidemia. J Sex Med 2011 Aug 2. doi: 10.1111/j.1743-6109.2011.02414.x. [Epub ahead of print]