Fat loss may be restored with dietary supplement

A dietary supplement called NucleomaxX restored modest amounts of arm and leg fat in people with lipoatrophy who were taking AZT or d4T at the same time, Dr Jussi Sutinen reported today at the Seventh International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, in Dublin, Ireland.

Although the causes of fat loss in people receiving antiretroviral treatment are still under investigation, there is increasing agreement that the nucleoside analogues d4T and AZT are major contributors to fat loss, and that their use is best avoided wherever possible.

But for people who have already suffered fat loss as a result of their treatment, repairing fat loss is currently difficult, with only one treatment licensed in Europe and North America that can repair facial fat loss. Fat restoration as result of switching from d4T or AZT to abacavir or tenofovir is very slow and often imperceptible to people who have experienced the fat loss during the first year after the treatment switch.

However, no one has yet identified a method of blocking the fat-destructive properties of d4T or AZT, which are presumed to be related to toxicity to mitochondrial DNA within the cells, leading to a complex process of fat cell shrinkage and destruction that is quite distinct in its microscopic signature from the fat loss caused by dieting or starvation.

Eighteen months ago German researcher Dr Ulrich Walker suggested that use of a supplement that could raise levels of uridine in the body might block some of the toxicity and give fat cells a chance to regenerate.

He collaborated with Finnish and US researchers to evaluate a supplement called NucleomaxX, which raises uridine levels and blocks some of the harmful effects of nucleoside analogue drugs used in cancer treatment. Dr Walker disclosed that he has applied for a patent with regard to uridine and the use of its precursors in the treatment of lipodystrophy.

In the Finnish study twenty people with lipoatrophy currently taking AZT or d4T were randomised to receive NucleomaxX or a placebo three times daily for ten days each month for three months. Participants had been receiving antiretroviral treatment for a median of 18 months.

Participants received DEXA and MRI scans in order to evaluate fat content of different body compartments at baseline and after three months of treatment.

After three months the group that received NucleomaxX had gained a significant amount of subcutaneous limb fat compared to baseline (approximately 900g), and that fat gain was significantly greater than any fat gain seen in the placebo group (pNucleomaxx group, but neither rose nor fell in the placebo group.

The improvement in limb fat seen after three months of NucleomaxX is similar to the improvement seen after more than one year in patients who switched from d4T to abacavir in the Mitox study, presented at the Lipodystrophy workshop in 2003.

The NucleomaxX group also gained a significant amount of intra-abdominal fat (approximately 200g), and again this change was significantly greater than any gain seen in the placebo group.

One patient dropped out of the NucleomaxX group due to the taste of the supplement, and after three months of treatment Dr Sutinen said that five of the nine patients receiving Nucleomaxx reported improvements in their lipoatrophy. “One or two” of the placebo group also reported improvement, Dr Sutinen said, which meant that there was no statistically significant difference between the groups in the proportions who reported an improvement.

Dr Grace McComsey of Case Western Reserve University, Cleveland, USA, reported on a 14 person open label study in which patients with lipoatrophy receiving d4T received NucleomaxX three times daily every other day for 16 weeks. They were then followed up for a further 16 weeks while taking their existing, d4T-containing regimen.

This study did not use DEXA or MRI scans to assess body fat distribution, so it is difficult to make comparisons between its findings and the Finnish study reported above, but after 16 weeks doctors and patients in the US study both reported significant improvement in lipoatrophy. Fat loss was graded 1 – 3 for each body area (arms, legs, buttocks, face), with a score of 3 for the most severe, and the maximum possible score was 12.

After 16 weeks the average patient-assessed improvement was 3.5 (8.0 to 4.5), and the average physician-assessed improvement was 3 (9.5 to 6.5). Improvement continued to week 32 despite the fact that participants were no longer taking NucleomaxX but still taking d4T.

The US study also assessed changes in mitochondrial DNA levels in subcutaneous fat by carrying out biopsies at week 16. Although there was a strong association between mitochondrial DNA levels and severity of lipoatrophy at baseline, this association had disappeared by week 16, suggesting to the investigators either that the amount of treatment necessary to produce improvements in lipoatrophy is considerably smaller than the amount needed to restore mitochondrial DNA levels, or that lipoatrophy is mot mediated by mitochondrial DNA levels.

In a discussion at the workshop Dr Sutinen suggested that NucleomaxX may not need to be dosed every day, indefinitely, and that the prolonged effect seen in both studies was a result of the `topping up` of the nucleotide pools in people who took the supplement. Participants in the Finnish study are now receiving open label treatment and will continue to be followed for at least six months.

It remains unclear whether this treatment will provide long-term sustained fat restoration, and it may not be appropriate for all people with lipoatrophy, particularly those who switched to other drugs in order to limit or repair the fat loss. People receiving ddI (didanosine) were specifically excluded from the Finnish study since ddI is a pyrimidine analogue.

Neither study reported any significant side effects apart from the unpleasant taste of the supplement, but after 12 weeks NucleomaxX recipients in the Finnish study had significantly lower HDL cholesterol levels, due both to a slight decline in HDL among NucleomaxX recipients and to an HDL increase in the placebo group. Lipid effects in the US study were not reported.

A larger US study sponsored by the US AIDS Clinical Trials Group is already underway.

Note

Anyone considering the use of this product as a treatment for lipoatrophy should consult their physician; self-medication is not recommended. The studies here were only performed on individuals receiving AZT or d4T, and the benefits and toxicities are unknown in individuals not currently taking AZT or d4T.