Men who have been in serious long-term relationships are familiar with a certain scenario: if it is cold outside, your wife or girlfriend is apt to put her hands or feet on you or under you. If you're in bed, this can be a rude way to wake up, akin to having an ice cube put on your skin!

Why do they do that?!

The ladies know: their hands and feet are friggin freezing! They're just looking for a way to warm them up.

It's established that women are more sensitive than men to temperature deviations, particularly cooler conditions. There are several reasons why this might be, including differences in reproductive hormones (e.g., estrogens promote a lower body temperature) and in the nervous systems. Indeed, the nervous system may be the big culprit during acute experience of cold extremities, as it can over-react and excessively lower circulation. It may be an evolutionary defensive mechanism to protect the baby at the cost of the mother.

Raynaud's Phenomenon

This reaction can result in Raynaud's Phenomenon, where a temperature change causes nearly complete shutdown of blood flow to the extremity. This can cause the afflicted area to turn white and go numb. While most common in fingers and toes, it can happen to the ears, nose, and even tongue and nipples! In the most severe cases (which thankfully are very rare), blood loss to the area can cause tissue damage, ulcerated wounds, and even require amputation.

Mild Raynaud's Phenomenon is surprisingly common, occurring in as many as 20-30% of women. The prevalence in men is much lower, perhaps only a few percent. You may have heard it called Raynaud's Disease or Raynaud's Syndrome, also known as Primary and Secondary Raynaud's, respectively. Disease or Primary means there is no other associated health condition and the Phenomenon exists on its own, and Syndrome or Secondary means there is an underlying issue (often a tissue disorder called sclerosis) that is causing the Phenomenon. For simplicity, I'll refer to it as Raynaud's since we're discussing phenomenon itself.

It was first described by Maurice Raynaud, a physician in the late 1800s. It is caused by excessive vasospasm, which is a sudden constriction of the blood vessels. Vasospasm can be bought on by an abrupt drop in temperature, vibration, or situational stress (like fear or anxiety). Current medical thought is Raynaud's is mostly related to hyperactivity of the sympathetic nervous system--the so-called 'flight-or-fight' response.

Indeed, Raynaud's sufferers have a startle response that doesn't decrease over time. In an experiment where subjects were exposed to a repeated stressor, like a loud noise or "bang" sound, over time a typical person will have a reduced sympathetic startle response, measured by steadily lowering vasoconstriction and racing heart beat after subsequent stressors. But a Raynaud's sufferer will continue to have the same startle response--their vasoconstriction and heart racing will be the same when exposed to a repeated startle stress, showing that there is an issue with the nervous system organization that would normally habituate to a 'fight-or-flight' stressor, whether a noise or cold temperature.

However, there's also a good bit of data that other, physiological issues with the blood vessels themselves are involved. A genetic component has been demonstrated in family and twin studies, showing that hypertension, migraine, Raynaud's phenomenon and coronary artery disease are all related to a single genetic factor. They haven't pinned down exactly what it is yet, but when they do it could stimulate further medical research.

What to do about it

OK, fine, but what should somebody do about it?

There are two over-arching treatment recommendations: stay warm and stop smoking.

Wow, thanks doc. *rolls eyes*

So, if you don't smoke and you're not willing to move closer to the equator, what can you do? Wear gloves all the time? Carry hot-packs in your pockets? Never drink beverages below 125 degrees Fahrenheit?

Obviously, taking pains to keep warm and protect against triggering events like abrupt cold transitions (like grabbing things from the freezer) is an important step. But what else can you do? Are there any medicines for Raynaud's?

Much to my surprise, there are _no_ approved drugs for Raynaud's. That is, no entity has run a controlled clinical trial and submitted a drug to the FDA and received approval for a treatment for Raynaud's. I find this shocking! What has occurred are a lot of independent clinical trials by academic researchers testing drugs for other, related cardiovascular diseases for their effects in Raynaud's. This has lead to a lot of knowledge about the biology behind Raynaud's and what might work--but again, there isn't any drug robustly proven to make a difference and approved for use in Raynaud's by the FDA.

Scientists believe that there are four physiological areas that should be addressed to try and alleviate Raynaud's:

Reduce vasospasm (prevent closing of the blood vessels)
Increase vasodilation (open up the blood vessels)
Reduce blood vessel damage (heal and make them work better)
Reduce blood viscosity (make it thinner so it flows better)

Reducing vasospasm

The narrowing of blood vessels and increase of blood pressure is a natural result of activation of the sympathetic 'fight-or-flight' nervous system. Since people who experience Raynaud's seem to have a hyperactive 'fight-or-flight' response, dampening this type of signaling may have benefits. A number of high-blood pressure medicines appear to help Raynaud's, including calcium channel blockers, endothelin receptor antagonists, angiotensin-converting-enzyme inhibitors, and angiotensin receptor blockers. However, beta-blockers, which are occasionally used for hypertension and block sympathetic nerve signalling, can make Raynaud's worse. Go figure.

Since the 'fight-or-flight' response is essentially a stress response, reducing stress could be another path to reducing vasospasm and Raynaud's. In fact certain medicines for depression and anxiety that exert calming effects (like Prosac, a serotonin reuptake inhibitor) have been shown to help Raynaud's.

However, I didn't find any support that non-pharmacological nervous system manipulation (for example, psychotherapy or meditation) helped with Raynaud's, but those approaches may also be worth a shot.

Increasing vasodilation

If a door is open wide, it takes longer for it to close. By the same principle, if you can open up your blood vessels, when you have a vasospasm perhaps the effects won't be as severe.

The first step is avoiding those things that naturally constrict blood vessels. Caffeine and nicotine are the big ones here. So if you like the old-fashioned cafe culture of coffee and cigarettes, you may want to change your lifestyle. Migraine medicines (such as ergotamine) also can act by constricting blood vessels, as do many over-the-counter cold and allergy medicines. Diet aids such as yohimbine also have this narrowing effect.

The next step is to consider drugs that may be helpful by causing vasodilation. Many cardiovascular medicines work in this fashion. The most common mechanism is increasing the levels of nitric oxide in the blood. Nitric oxide (NO) should not to be confused with nitrous oxide, an anaesthetic you may have (illegally) played around with in your foolish youth. NO is an important cellular signalling molecule that tells the blood vessels to relax and let more blood through.

The classic way to increase NO is by using precursors, such as nitroglycerin or nitrites. People afflicted with angina, which is chest pain due to poor circulation around the heart, often take nitroglycerin pills. Treatment increases blood NO, relaxes vessels around the heart, increases blood flow to the heart muscles, and reduces the chest pain. Oral nitroglycerin pills have had mixed success treating Raynaud's, but topical nitroglycerin (in a cream, for example) applied to afflicted extremities can reduce the severity and frequency of attacks.

You might find it interesting that Viagra was originally developed for angina! Viagra contains a drug that increases blood NO by blocking the enzyme that breaks NO down. The apocryphal legend is that the elderly men who participated in the clinical trial didn't experience any relief of their angina, but refused to give any of the leftover medicine back. When asked why, they revealed the unintended side effect of sustained erections. Clearly, Viagra increased blood flow to peripheral parts of the body. Talk about a happy coincidence for everybody involved!

But wait, you may be saying, if Viagra increases NO in extremities, and NO widens blood vessels, and NO helps Raynaud's, would Viagra treat Raynaud's? Yes! There is good data that Viagra, Cialis, and other erectile dysfunction drugs could aleviate Raynaud's symptoms. However, these drugs are not without risks, and side effects are quite possible.

There are also over-the-counter ways to increase blood NO. The amino acid arginine is the body's natural precursor to NO. Arginine is used as a supplement by body builders to get a big "pump" during a workout, because in high doses it will increase NO and blood flow and make them look veiny (which apparently is desirable). Arginine's benefits in Raynaud's have been mixed, perhaps because it undergoes a great deal of metabolism when ingested: about half of the arginine you ingest is broken down and excreted without any effect on NO. Citrulline, on the other hand, is a precursor to arginine and may be more effective because more of it makes it into the blood and thus can be converted into arginine and eventually into NO. However, citrulline too has had mixed results in clinical trials.

Last but not least in the vasodilation category, there are omega-3 fatty acids, particularly fish oil. Personally, I'm a fan of getting my O3s from food (like fish), but there is robust evidence of the efficacy for O3s to benefit cardiovascular function. In fact, there are approved O3 drugs for treatment of cardiovascular disease, so it's pretty clear there is a pharmacological effect. To summarize an insanely complex area of biology: O3 fats are mostly anti-inflammatory, whereas Omega-6 fats are mostly pro-inflammatory. Chronic inflammation can narrow blood vessels (so avoiding inflammation is good for Raynaud's). Increasing the amount of O3s ingested can reduce inflammation, and open up blood vessels. So, eating fish and/or taking fish oil could potentially be helpful for Raynaud's.

A wrinkle to that assertion is evening primrose oil, which contains gamma-Linolenic acid (GLA). GLA is an O6 fat, but it has anti-inflammatory effects. Say what? Yeah, don't get caught up on that. There have been some studies that suggest it could have beneficial effects in Raynaud's, but don't use that to conclude that its OK to eat vegetable oils (high in O6)...it's probably not.

Heal your blood vessels

As you age, your blood vessels stiffen up from accumulated damage from reactive oxygen species, cholesterol particles, inflammation, and other assaults. This stiffening prevents the blood vessels from responding to signals to relax, leading to high blood pressure and potentially increased susceptibility to Raynaud’s. Furthermore, the blood vessels themselves generate NO, and when damaged produce less NO, which as described above is potentially an exacerbator of Raynaud’s symptoms.

Removing the causes of the damage can encourage healing of the blood vessels and restore some of their function. The big problems are smoking and over nutrition. Both lead to extensive exposure to oxidants and toxic intermediates that damage the blood vessels, as well as the brain and the rest of the body. It’s well beyond the scope of this article, but suffice it to say that you should not smoke and you should eat nutrient-dense food in amounts that maintain a healthy bodyweight.

The only therapy proven to work in this regard? Exercise. Physical exertion is naturally anti-oxidant, burns excess energy, reduces systemic inflammation, and promotes healing. If exercise could be packaged in a pill, it would literally be considered a “miracle drug.”

Vitamins and anti-oxidant pills, while looked at as the holy-grail by many, have never been shown to increase health or decrease disease (besides micronutrient deficiencies obviously). In fact, many studies have show that excessive vitamins and anti-oxidants may cause some diseases, such as certain cancers. Eat your fruits and veggies, but skip the mega-dose multis.

Thin your blood

Pretend there are two pitchers of the same shape in front of you. In one of them, water. In the other, molasses. If you were to pour them out in the same way, which one would empty first?

Right. The viscosity of a fluid affects its flow. Similarly, if your blood is thick, it won’t flow as well, making it harder for the blood to get through constricted vessels, making Raynaud’s worse. Therefore, thinning the blood may help Raynaud’s.

Perhaps the simplest way to do this is avoid dehydration. In the winter months, the air is dry and as a result so are we. Drinking a lot of water all day long increases your overall body fluid and helps blood flow.

You may have heard that medical experts recommend low-dose (so-called “baby”) aspirin as a preventative measure for cardiovascular disease. One of the ways aspirin works by blocking the binding of platelets to each other, preventing blood clots and thereby thinning the blood. Thus, it may have benefits in Raynaud’s. Of course, aspirin can be very hard on the stomach and cause ulcers; no therapy (perscription or over-the-counter) is without risk.

Fish oil also helps thin the blood in addition to improving vasodilation, so that’s a second reason to eat more fish.

Talk to your doctor

As always, talk to your doctor. While Raynaud's Phenomenon is shockingly common, it can also be an indicator of more substantial physiological problems. But if you are afflicted with Primary Raynaud's, hopefully the above will give you more to talk to your doctor about after she gives you the simple admonition to "keep warm."

If all else fails

You can always move to Key West, the closest you can get to the equator in the continental USA!