Sometimes small LDL is the only abnormality

Janet is a 58-year old schoolteacher. At 5 ft 3 inches and 104 lbs, she had barely an ounce of fat on her size-2 body. For years, Janet's primary care physician complimented her on her cholesterol numbers: LDL cholesterol values ranging from 100 to 130 mg/dl; HDL cholesterol of 50-53 mg/dl.

Yet she had coronary disease. Her heart scan score: 195.

Lipoprotein analysis uncovered a single cause: small LDL. 95% of all of Janet's LDL particles were in the small category. What was surprising was that this pattern occurred despite her slender build. Weight is a powerful influence on the small LDL pattern and the majority of people with it are overweight to some degree. But not Janet.

How did she get small LDL if she was already at or below her ideal weight? Genetics. Among the genetic patterns that can account for this pattern is a defect of an enzyme called cholesteryl-ester transfer protein, or CETP. This is the exact step, by the way, that is blocked by torcetrapib, the new agent slated for release sometime in future (The manufacturer, Pfizer, is apparently going to sell this agent only packaged in the same tablet as Lipitor. This has triggered an enormous amount of criticism against the company and they are, as a result discussing marketing torcetrapib separately.)

Also note that Janet had a severe excess of small LDL despite an HDL in the "favorable" range. (See my earlier conversation on this issue, The Myth of Small LDL at http://drprevention.blogspot.com/2006/06/myth-of-small-ldl.html.)

With Janet, weight loss to reduce small LDL was not an option. So we advised her to take fish oil, 4000 mg per day; niacin, 1000 mg per day; vitamin D, 2000 units per day; use abundant oat bran and raw almonds, both of which suppress small LDL. This regimen has--surprisingly--only partially suppressed her small LDL pattern by a repeat lipoprotein analysis we just performed. We're hoping this may do it, i.e., stop progression or reduce her heart scan score.

The lesson: Small LDL is a very potent pattern that can be responsible for heart disease, even if it occurs in isolation. And, contrary to conventional thinking, small LDL can occur as an independent abnormality, even when HDL is at favorable levels.
Loading
Melatonin for high blood pressure?

Melatonin for high blood pressure?

Melatonin is fascinating stuff.

In addition to its use as a sleep aid, melatonin exerts possible effects on cardiovascular parameters, including anti-oxidative action on LDL, reduction in sympathetic (adrenaline-driven) tone, and reduction in blood pressure.

Several studies document the blood pressure-reducing effect of melatonin:

Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension.

Melatonin reduces night blood pressure in patients with nocturnal hypertension.

Prolonged melatonin administration decreases nocturnal blood pressure in women.

Blood pressure-lowering effect of melatonin in type 1 diabetes.


But blood pressure may be increased when melatonin is added to nifedipine, a calcium channel blocker:

Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study.


Effects on BP tend to be modest, on the order of 5-8 mmHg reduction in systolic, half that in diastolic.

But don't pooh-pooh such small reductions, however, as small reductions exert mani-fold larger reductions in cardiovascular events like heart attack and stroke. NIH-sponsored NHANES data (see JNC VII), for example, document a doubling of risk for each increment of BP of 20/10. The Camelot Study demonstrated a reduction in cardiovascular events from 23% in placebo subjects to 16.7% in subjects taking amlodipine (Norvasc) with a 5 mm reduction in systolic pressure, 2 mmHg drop in diastolic pressure. Small changes, big benefits.

Many people take melatonin at bedtime and are disappointed with the effects. However, a much better way is to take melatonin several hours before bedtime, e.g., take at 7 pm to fall asleep at 10 pm. Don't think of melatonin as a sleeping pill; think of it as a sleep hormone, something that simply prepares your body for sleep by slowing heart rate, reducing body temperature, and reducing blood pressure. (You may need to modify the interval between taking melatonin and sleep, since individual responsiveness varies quite a bit.)

I also favor the sustained-release preparations, e.g., 5 mg sustained-release. Immediate-release, while it exerts a more rapid onset of sleep, allows you to wake up prematurely, The sustained-release preparations last longer and allow longer sleep.

The dose varies with age, with 1 mg effective in people younger than 40 years, higher doses of 3, 5, even 10 or 12 mg in older people. Sustained-release preparations also should be taken in slightly higher doses.

The only side-effect I've seen with melatonin is vivid, colorful dreams. Perhaps that's a plus!

Comments (15) -

  • Jeanne Shepard

    5/10/2008 2:27:00 PM |

    I've hears that you can take melatonin too long, that is build up a tolerance.
    Any thoughts? I prefer it to other sleep aides, otherwise.

  • Anonymous

    5/10/2008 9:15:00 PM |

    After reading the article, I'm going to give melatonin a try.  Bought a bottle of 1mg tablets.

  • Michael

    5/10/2008 11:09:00 PM |

    I don't know if I have a weird body or something, but melatonin doesn't agree with me at all. It makes me a tiny bit groggy when I take it, but it turns me into a zombie the next day. Even small doses, like 1-2grams, basically makes me feel like I didn't sleep at all that night, and I feel crummy all day.

  • Jenny

    5/11/2008 11:33:00 AM |

    Dr. Davis,

    I have taken melantonin for many years and it helps me not only sleep, but get back to sleep if I wake up in the middle of the night.

    I've found a huge difference in the effectiveness of various company's pills. Trader Joe's for example, don't work for me at all. Schiff work very well.

    I was told years ago to take 1/4 of a pill for best results, and that is what I do. That works better than a larger amount for me.

  • Anne

    5/12/2008 1:10:00 AM |

    I have found melatonin to be very helpful. I go to sleep easily and I stay asleep. After I had bypass 8years ago, I was unable to sleep more than an 4-6 hours without Ambien. 8 months ago I started taking melatonin. It did not work right away, but after a few weeks I started to sleep very well and I have not had to restort to Ambien since. I take 3mg.

    I take 25mg metoprolol, a Beta blockers and found out that BB's decrease melatonin. Found this info through the internet, not my doctor.  

    My BP has been well controlled, even at night so I never checked to see if it went lower with melatonin.

  • Jeanne Shepard

    5/12/2008 3:24:00 AM |

    Jenny,

    Have you ever been told that you can't take it for a long period of time?
    I'd like to keep taking it, but was told not to.

    Jeanne

  • JohnN

    5/15/2008 2:01:00 AM |

    I have been taking melatonin for years and credit it with restorative sleep and general good health.
    Even so, my success rate is only about 70%. I discover that the amount of melatonin (in the blood) for a good night sleep (the desired effect) is a very small fraction of the oral dose that you can take. The difference is how the body (liver) metabolizes the substance. You really have to experiment to find the right dose for yourself; more is not better.
    For someone to try it for the very first time start at .1-.2 mg (a very small chunk of the tablet) and modify the dose accordingly.
    Do not think of it the same way as Ambien. It's best function is to ease you into sleep.
    Good luck.

  • Ann Theresa

    9/27/2008 1:59:00 PM |

    I am so hot at night that when I sleep, I wake up because of it.  I started taking my blood pressure upon waking and found it to be high.  160 or so over  90-95. I could feel the way my body felt. My blood pressure during the day is usually 115-120 over 70.  I knew I was peri menepausal, so the hormone thing was very suspect. After a lot of research, I decided to start taking 3 mg Melatonin. I checked with my doctor and he was catching up with me on his computer as we spoke.It was funny!  But anyway....I have been on these for about 3-4 weeks now and find that although I'm still warm when sleeping,  I am in a deeper sleep. My blood pressure now upon waking is about 123-125 over 82-83.  I have seen a significant improvement in lower blood pressure.  I will add that I have been walking daily and started taking a B complex also before bed.  I take my melatonin just before bedtime.  I have never had any problems with falling asleep. So the timing of use should be adjusted for when you need it.  I would much rather take this hormone than take the blood pressure medicine my doctor was so fast to offer.

  • Anonymous

    11/10/2008 7:54:00 PM |

    I swear by melatonin, and recommend the 5mg time release.  For me, it works best if I take it about 30 minutes before bedtime.  The time release eliminates the problems with waking up too early.

    The only time I have problems with feeling groggy is when I don't get enough sleep.  If you take it at midnight, then get up at 5 am, you're going to feel it.  If I know I'm not going to get at least 7-8 hours of sleep, I will skip the melatonin that night so I don't feel groggy.

    I have seen extreme differences in brands, so I think there is something to the comments about the quality of different manufacturers.

    I've never been told not to take it over long periods, but then I didn't ask a doctor about it.  I've noticed a slight tolerance if you take it all the time, so I sometimes will stop taking it for a while to break that cycle.

  • Improve Health Heart

    4/10/2009 3:43:00 PM |

    Hello.

    Your post looks quite interesting.. I never knew that Melatonin is a substance which has such uses.. I had heard of the term anywhere in any book but never took much interest in it..

    But your post spills out quite knowledgeable information definitely this much that it will hold my attention for a long long time..

    I also have a great interest in Heart related issue's and I have created a blog myself for it..

    I hope my posts will also help you gain some info..

  • Jonathan Byron

    4/22/2009 2:44:00 PM |

    There is some interesting research that suggests that melatonin is one factor that reduces insulin secretion at night.

  • TedHutchinson

    9/6/2009 6:26:07 PM |

    Oxidized-LDL and Fe3+
    /Ascorbic Acid-Induced Oxidative
    Modifications and Phosphatidylserine Exposure in Human
    Platelets are Reduced by Melatonin

    Abstract.
    Low-density lipoprotein (LDL) modifications and platelet activation are major risk factors for cardiovascular diseases. When platelets are exposed to oxidative stress, they become activated. Oxidized LDL (ox-LDL) and metal-catalysed oxidation systems such as Fe3+/ascorbic acid increase free radical production.
    We wanted to verify whether melatonin has a protective effect against oxidative modifications and phosphatidylserine externalization in platelets induced by ox-LDL and Fe3+/ascorbic acid.....snip.... These data suggest that melatonin may protect platelets from iron overload-induced and ox-LDL-induced
    oxidative modifications and also from the triggering signals of apoptosis activation, possibly due to its scavenger effect on toxic free radicals.

    The full text of both abstract and paper are the link above.

  • Serg

    7/21/2010 5:52:26 PM |

    This article regarding Melatonin for high blood pressure? is very interesting and useful, blood pressure may affect your sexual activity, and this not only happen to older people as I used to believed, young people can also be affected so you may need  to buy viagra to help yourself on those situations.

  • buy jeans

    11/3/2010 4:54:14 PM |

    I also favor the sustained-release preparations, e.g., 5 mg sustained-release. Immediate-release, while it exerts a more rapid onset of sleep, allows you to wake up prematurely, The sustained-release preparations last longer and allow longer sleep.

  • mike

    2/22/2011 11:37:17 AM |

    One such remedy that has gained popularity in recent years is melatonin. Melatonin is a growth hormone naturally produced by the pineal gland in your brain. Melatonin hormones are secreted at night or in the dark and helps regulate the sleeping cycle. It is believed that melatonin may help the body know when it is time to go to sleep and when it's time to wake up. These days, melatonin can be taken in pill form to treat everything from jet lag to insomnia. However, like with all medications, there is the potential for serious melatonin side effects if take with other medications.

    Reference:
    melatonin usage consider your age

    melatonin side effects

Loading